SORAFENIB FOR OSTEOSARCOMA CELLS

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SORAFENIB FOR OSTEOSARCOMA CELLS

Posted On : Jan-20-2012 | seen (419) times | Article Word Count : 595 |

INTRODUCTION

Two vital pathways are stimulated via RTK or receptor tyrosine kinase. These pathways include the PI3K which is progressed through AKT and secondly mitogen activated protein (MAP) kinase pathway which depends on ERK1/2 for its progress. MAP kinase pathway is very important for the cell growth and survival and when this is hyperactivated it leads to the vast variety of malignancies. This pathway is initiated from Ras and procedes via Raf-MEK1, MEK2-ERK1, ERK2. Various novel inhibitors of these vital pathways are discovered via high throughput screening which show their anti-cancer properties. Sorafenib is one these vital kinase inhibitor which inhabits the MAP kinase pathway.

Bone tumor or osteosarcoma is characterized due to its high metastasis rate. Various reasons like the over expression of P-glycoprotein resulted in the failure of many chemotherapeutic compounds in treatment of this type of malignancy. As the RTKs are vital for cancer cells, chemical libraries were examined in order to find a novel agent which may target these kinases. The metastasis of Osteosarcoma and rhabdomyosarcoma have role of various RTKs including VEGFR-2, VEGFR-3, KIT and PDGFR-?. In addition to this, Ezrin a linker protein which is present in cytoskeleton is important for metastasis and this protein is a member of ERM family. The tumerogenesis process is proceeded by metalloproteinases-2 and 9 present in the matrix. In early studies it was assumed that Sorafenib acts on the Raf kinases (RAF-1, BRAF and BRAF V600E) in order to hinder the MAPK pathway. Further studies proved the broad spectrum effect of this compound as it also inhibits the RTKs so it is a RTK inhibitor and checks the angiogenesis and tumor progression. One another action of this compound has noticed as it also inhibits the MCL-1 anti-apoptotic protein leading to apoptosis of tumor cells. Sorafenib is based on Biarylureic structure and proved to be effective in kidney, liver and thyroid gland associated cancers. This agent is active in both in vivo and in vitro conditions can target ERM, MCL-1 and ERK1/2 pathways as reported during pre-clinical studies. Hence it is an angiogenesis inhibitor which has the tendency to stop the tumor cell proliferation or metastasis.

FUNCTION OF SORAFENIB IN ADVANCED MELANOMA

Sorafenib effects on the advanced metastatic melanoma were studied during the clinical trials phase II. It was reported that this inhibitor had poor effects when used alone. It was found that Sorafenib activity did not relate to the BRAFV600E mutation, proving that it is not specific for BRAF gene in addition to this cyclin D1 and Ki67 also did not affected prominently. These findings provided the clue about its multiple targets.

During clinical evaluation it was found that Sorafenib has some side effects as under physiological conditions secondary erythrocytes production is increased. Another common name of this condition is erythropoiesis which ultimately leads to the anemia slowly. Certain other inhibitor like doxorubicin is also used in combination with Sorafenib for the treatment of advanced stage hepatocellular carcinoma. It was also effective for this carcinoma when used alone. Like other many inhibitors it also shows its effectiveness when used in a increasing dose manner. The catabolism of this compound takes place in liver cells via UDG-transferase1A9 and Cyt P4503A4.

CONCLUSION

In a nut shell, Sorafenib a kinase inhibitor with wide range of targets. It is very effective in case of metastatic cancers of bone ect. It is under phase II of clinical trials and is being analyzed for its pharmacological properties. This inhibitor is promising as it has the ability to induce apoptosis of cancerous cells.

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<h1>SORAFENIB FOR OSTEOSARCOMA CELLS</h1> Author: <a href='http://www.articleseen.com/profile_Dr.Rabia.aspx'>Dr.Rabia</a> INTRODUCTION

Two vital pathways are stimulated via RTK or receptor tyrosine kinase. These pathways include the PI3K which is progressed through AKT and secondly mitogen activated protein (MAP) kinase pathway which depends on ERK1/2 for its progress. MAP kinase pathway is very important for the cell growth and survival and when this is hyperactivated it leads to the vast variety of malignancies. This pathway is initiated from Ras and procedes via Raf-MEK1, MEK2-ERK1, ERK2. Various novel inhibitors of these vital pathways are discovered via high throughput screening which show their anti-cancer properties. Sorafenib is one these vital kinase inhibitor which inhabits the MAP kinase pathway.

Bone tumor or osteosarcoma is characterized due to its high metastasis rate. Various reasons like the over expression of P-glycoprotein resulted in the failure of many chemotherapeutic compounds in treatment of this type of malignancy. As the RTKs are vital for cancer cells, chemical libraries were examined in order to find a novel agent which may target these kinases. The metastasis of Osteosarcoma and rhabdomyosarcoma have role of various RTKs including VEGFR-2, VEGFR-3, KIT and PDGFR-?. In addition to this, Ezrin a linker protein which is present in cytoskeleton is important for metastasis and this protein is a member of ERM family. The tumerogenesis process is proceeded by metalloproteinases-2 and 9 present in the matrix. In early studies it was assumed that Sorafenib acts on the Raf kinases (RAF-1, BRAF and BRAF V600E) in order to hinder the MAPK pathway. Further studies proved the broad spectrum effect of this compound as it also inhibits the RTKs so it is a RTK inhibitor and checks the angiogenesis and tumor progression. One another action of this compound has noticed as it also inhibits the MCL-1 anti-apoptotic protein leading to apoptosis of tumor cells. Sorafenib is based on Biarylureic structure and proved to be effective in kidney, liver and thyroid gland associated cancers. This agent is active in both in vivo and in vitro conditions can target ERM, MCL-1 and ERK1/2 pathways as reported during pre-clinical studies. Hence it is an angiogenesis inhibitor which has the tendency to stop the tumor cell proliferation or metastasis.

FUNCTION OF SORAFENIB IN ADVANCED MELANOMA

Sorafenib effects on the advanced metastatic melanoma were studied during the clinical trials phase II. It was reported that this inhibitor had poor effects when used alone. It was found that Sorafenib activity did not relate to the BRAFV600E mutation, proving that it is not specific for BRAF gene in addition to this cyclin D1 and Ki67 also did not affected prominently. These findings provided the clue about its multiple targets.

During clinical evaluation it was found that Sorafenib has some side effects as under physiological conditions secondary erythrocytes production is increased. Another common name of this condition is erythropoiesis which ultimately leads to the anemia slowly. Certain other inhibitor like doxorubicin is also used in combination with Sorafenib for the treatment of advanced stage hepatocellular carcinoma. It was also effective for this carcinoma when used alone. Like other many inhibitors it also shows its effectiveness when used in a increasing dose manner. The catabolism of this compound takes place in liver cells via UDG-transferase1A9 and Cyt P4503A4.

CONCLUSION

In a nut shell, Sorafenib a kinase inhibitor with wide range of targets. It is very effective in case of metastatic cancers of bone ect. It is under phase II of clinical trials and is being analyzed for its pharmacological properties. This inhibitor is promising as it has the ability to induce apoptosis of cancerous cells.About the Author: As one of the world leading suppliers of high-performance life-science products. We have over 8,000 products which consist of inhibitors, antibodies, RNAis, proteins and peptides those which focus on signaling pathways such as <a rel="nofollow" href="http://www.selleckchem.com/products/AZD6244.html">AZD6244</a>, <a rel="nofollow" href="http://www.selleckchem.com/products/AZD5438.html">AZD5438</a>, <a rel="nofollow" href="http://www.selleckchem.com/screening-libraries.html">Chemical Libraries</a> & so on. Furthermore, compound libraries for Article Source: <a href='http://www.articleseen.com/Article_SORAFENIB-FOR-OSTEOSARCOMA-CELLS_136637.aspx'> http://www.articleseen.com/Article_SORAFENIB FOR OSTEOSARCOMA CELLS_136637.aspx</a>

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As one of the world leading suppliers of high-performance life-science products. We have over 8,000 products which consist of inhibitors, antibodies, RNAis, proteins and peptides those which focus on signaling pathways such as AZD6244, AZD5438, Chemical Libraries & so on. Furthermore, compound libraries for

Keywords : AZD6244, AZD5438,

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